Role of interferons and other cytokines in the regulation of the immune response

Abstract

Belardelli, E Role of interferons and other cytokines in the regulation of the immune response. APMIS 103: 161-179, 1995. Cytokines represent the major factors involved in the communication between T cells, macrophages and other immune cells in the course of an immune response to antigens and infectious agents. A number of studies on mouse and human T helper (Th) clones have recently provided extensive evidence for the existence of different activities exhibited by Th cells (called Thl and Th2), which was apparently inferred from the profile of cytokine secretion. The Th 1 -type immune response is generally associated with IgG2a production and the development of cellular immunity, the Th2-type response with IgE production, eosinophils and mast cell production. This review focuses on the role of different cytokines produced by macrophages (especially interferons (IFNs), TNF-a, IL-10 and IL-12) or T cells (IFNs, IL-2, IL-4, IL-10, IL-13 and TGF-P) in macrophage-T cell interactions and the cytokine relevance in the differentiation of Th cells towards the Thl or Th2 type of immune response. Thlderived cytokines (IFN-gamma, IL-2, TNF-a) favor macrophage activation, whereas the Th2 cytokines (IL-4, IL-10, IL-13) exhibit suppressive activities on macrophage functions. A key role in the differentiation towards the Thl -type response is now attributed to IL-12, a recently described cytokine produced mainly by macrophages. Its production can be upregulated by IFN-gamma and is inhibited by IL-10 and IL-4. All this emphasizes the importance of macrophage-cytokine interactions in determining the type of immune response. This article also aims to review recent data concerning the roles of IFNs a@ (type I) and IFN-gamma (type 11) in the regulation of the immune response. While there is much information on the regulatory effects of IFN-gamma (also called "immune IFN") on the immune response, little is so far known of the role of type I IFNs. These cytokines, originally described as simple antiviral substances, are now taken to be important regulators of the immune response. Recent data indicate that these molecules (especially IFNs-a) specifically promote the differentiation towards the Thl-type response. The stimulatory effects of IFN-a on the generation of the Th I-type response may be involved in its therapeutic effects in some human diseases, including early AIDS, hypereosinophilia and certain tumors. It is reasonable to assume that, with the increasing interaction between basic and clinical research, considerably more will be understood about how IFNs and other cytokines interact in the modulation of the immune response, and how this knowledge can be successfully translated into new and more selective therapeutic strategies against human diseases.Cytokines are now widely accepted to be the major factors involved in the regulation of the immune response to antigens and infectious agents. As new members of the cytokine family are being identified and characterized, understanding their role in the regulation of the immune r...

Differential effects of angiostatin, endostatin and interferon-α1 gene transfer on in vivo growth of human breast cancer cells

“…In fact, type I IFNs exert multiple regulatory activities on host immune cells that are particularly relevant to the overall antitumor response. 25,26 We did not detect a more intense lymphoid infiltrate in IFN-␣ 1 -producing tumors compared with controls or angiostatin-or endostatin-producing tumors. Furthermore, we tested the susceptibility of MCF7 and MDA-MB435 cells to NK-mediated lysis in vitro, and found that neither was efficiently killed by activated murine NK cells (data not shown).…”

Type I consensus interferon (CIFN) gene transfer into human melanoma cells up-regulates p53 and enhances cisplatin-induced apoptosis: implications for new therapeutic strategies with IFN-alpha

“…In fact, type I IFNs exert direct effects on tumor cells, such as the down-regulation of oncogene expression and induction of tumor suppressor genes, which can contribute to the antiproliferative activity of these cytokines, and the increase of MHC class I expression, which can enhance immune recognition. 5,6 Moreover, type I IFNs also have important immunoregulatory functions, promoting macrophage differentiation, increasing NK cells and CD8 + CTL cytotoxicity, and favoring the differentiation of type 1 T helper cells (reviewed in Ref. 6).…”

“…5,6 Moreover, type I IFNs also have important immunoregulatory functions, promoting macrophage differentiation, increasing NK cells and CD8 + CTL cytotoxicity, and favoring the differentiation of type 1 T helper cells (reviewed in Ref. 6).…”

Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity

“…These data indicate that bi-MoAb OKT3/NSI19-9 in combination with anti-CD28 MoAb 15E8 induces the release of cytokines that were shown by others to be capable of mediating a cellular immune response [8][9][10]. To exclude the potential influence of residual Fc receptor-bearing cells, all assays for specific T cell activation were conducted in the presence of 20% human serum that was shown to efficiently block Fc receptor-mediated, non-specific MoAb presentation via IgG Fcg [19,20].…”

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